ZnIn2S4　(noted　as　ZIS)　has　great　potential　in　tetracycline　degradation　due　to　its　suitable　band　gap　structure　and　great　light　absorption　capability.　However,　its　serious　photo-corrosion　results　in　the　deactivation　of　photo-catalytic　activity.　In　this　work,　we　try　our　best　to　probe　the　deactivation　and　regeneration　of　ZnIn2S4　in　photocatalytic　degradation　of　tetracycline.　EPR,　XPS,　and　PL　results　reveal　that　the　deactivation　mechanism　of　ZIS　is　due　to　the　breakage　of　Zn-S　bonds　which　results　in　excessive　sulfur　vacancies.　After　choosing　Na2S　as　regenerant,　the　degradation　rate　in　second　cycle　increased　from　57.4　%　to　88.1　%　and　improved　from　30.3　%　to　76.8　%　in　third　cycle.　Ab　initio　molecular　dynamics　simulations　(AIMD)　and　density　functional　theory　(DFT)　calculations　are　further　conducted　for　the　regeneration　mechanism.　These　results　confirm　that　the　negatively　charged　ions　(HS-and　OH-ions)　produced　by　hydrolysis　of　the　Na2S　are　attracted　to　the　positively　charged　sulfur　vacancies,　promoting　the　re-bonding　of　Zn-S　bonds　and　thereby　relieve　excessive　sulfur　vacancies.　This　work　not　only　provides　a　detailed　discussion　of　performance　deactivation　caused　by　photo-corrosion　of　ZnIn2S4　but　also　offers　new　insights　into　the　regeneration　mechanism　of　ZnIn2S4.